Loss of CDKN2A and p14ARF expression occurs frequently in human nonmelanoma skin cancers

A. Pacifico, L. H. Goldberg, K. Peris, S. Chimenti, G. Leone, H. N. Ananthaswamy

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Background: The CDKN2A locus on human chromosome 9p21 encodes two proteins named p16INK4a and p14ARF, known to function as tumour suppressors via the retinoblastoma (Rb) or the p53 pathway. The p53 tumour suppressor gene is the most commonly mutated gene in human and mouse cancers. Disruption of the p53 and Rb pathways is a fundamental trend of most human cancer cells. Recent studies have shown that the CDKN2A gene plays an active role in the p53 and Rb tumour suppressor pathways. Genetic abnormalities in CDKN2A have been well documented in human melanoma, but their involvement in nonmelanoma skin cancer (NMSC) is less clear. Objectives: To determine whether genetic abnormalities in CDKN2A and p53 genes play a role in the development of NMSC. Methods: We analysed 40 primary NMSCs in 40 patients (21 squamous cell carcinomas, 17 basal cell carcinomas and two actinic keratoses) for p16 INK4a and p14ARF protein expression and for genetic alterations in exons 1α, 1β and 2 of CDKN2A. Results: Immunohistochemical analysis revealed loss of expression of p16INK4a and p14ARF proteins in 38 and 39 of 40 NMSCs, respectively. Amplification of genomic DNA by polymerase chain reaction revealed homozygous deletion of exon 1β in 20% of tumours and of exon 2 in 82.5% of tumours. Of 22 NMSCs with p53 mutations, 13 (59%) had ultraviolet (UV) signature mutations in the p53 gene; all of them were strongly positive for p53 immunostaining. Conclusions: In addition to mutations in the p53 gene, loss of expression of CDKN2A via deletion also plays an important role in the pathogenesis of human NMSC. While p53 mutations are induced by UVB, deletions in CDKN2A could arise spontaneously, perhaps during tumour progression.

Original languageEnglish (US)
Pages (from-to)291-297
Number of pages7
JournalBritish Journal of Dermatology
Issue number2
StatePublished - Feb 2008


  • Gene silencing
  • Homozygous deletion
  • Skin neoplasms
  • Tumour suppressor gene

ASJC Scopus subject areas

  • Dermatology


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